Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Injury Risk Functions for the Midsized Male Wrist and Elbow as a Result of Behind Shield Blunt Trauma.

Ballistic shields protect users from a variety of threats, including projectiles. Shield back-face deformation (BFD) is the result of the shield deflecting or absorbing a projectile and deforming toward the user. Back-face deformation can result in localized blunt loading to the upper extremity, where the shield is supported by the user. Two vulnerable locations along the upper extremity were investigated-the wrist and elbow-on eight postmortem human subjects (PMHS) using a pneumatic impacting apparatus for investigating the fracture threshold as a result of behind shield blunt trauma (BSBT). Impacting parameters were established by subjecting an augmented WorldSID anthropomorphic test device (ATD) positioned behind a ballistic shield to ballistic impacts. These data were used to form the impact parameters applied to PMHS, where the wrist most frequently fractured at the distal radius and the elbow most frequently fractured at the radial head. The fracture threshold for the wrist was 5663±1386 N (mean±standard deviation), higher than the elbow at 4765±894 N (though not significantly, p = 0.15). The failure impact velocity for wrist impacts was 17.7±2.1 m/s, while for the elbow, the failure impact velocity was 19.5±0.9 m/s. An approximate 10% risk of fracture threshold was identified on the modified WorldSID ATD (no flesh analogue included) to inform future protective standards.

[Diagnosing neuropathic orofacial pain in the general dental practice]. / Diagnosticeren van neuropathische orofaciale pijn in de algemene tandartspraktijk.

Dental pain is a common reason for patients to visit the dentist. This type of pain is usually easy to diagnose and treat. However, diagnosing and treating other forms of orofacial pain remains complicated. One of the most challenging types of orofacial pain to diagnose and treat is neuropathic orofacial pain: pain resulting from damage to nerve tissue. Recognizing this type of pain in a timely manner can prevent unnecessary invasive dental treatments and disappointment for patients who seek help for this type of pain. There are relatively simple tools for dentists to distinguish neuropathic pain from other types of orofacial pain. The treatment of neuropathic pain is primarily focused on symptom relief through medication.

The VACStent trial: combined treatment of esophageal leaks by covered stent and endoscopic vacuum therapy.

BACKGROUND: Endoscopic treatment of esophageal leaks, mostly by covered stents or endoscopic vacuum therapy (EVT), has largely improved the clinical outcome in the last decade. However, both techniques suffer from significant limitations. Covered stents are hampered by a high rate of migration and missing functional drainage, whereas endoluminal EVT devices are limited by obstruction of the GI tract. The new design of the VACStent makes it a fully covered stent within a polyurethane sponge cylinder, allowing EVT while stent passage is still open. Initial clinical applications have demonstrated the fundamental concept of the VACStent. METHOD: A prospective multicenter open-label study was performed with the primary endpoint safe practicality, complete leak coverage, and effective suction-treatment of esophageal leaks. Secondary endpoints were prevention of septic conditions, successful leak healing, and complications, in particular stent-migration, local erosions and bleeding. RESULTS: Fifteen patients with different, mostly postoperative anastomotic leaks were enrolled in three centers. A total of 41 VACStents were implanted. The mean number of VACStents per patient was 2.7, with a mean duration of VACStent treatment of 15 days. The primary endpoint was met in all VACStent applications (41/41 implants), resulting in a leak healing rate of 80% (12/15 patients). Septic episodes were prevented in 93% (14/15 patients) and there was no mortality. There were no severe device-related adverse events (SADE) nor significant local bleeding or erosion. Minor stent-dislocation and migration, respectively, was observed in 7%. Oral intake of liquids or food was documented in 87% (13/15 patients). One anastomotic stenosis was seen during follow-up. CONCLUSIONS: VACStent treatment is a safe and effective treatment in esophageal leaks which can be covered by the sponge cylinder. Its application was described as easy and resembling that of conventional GI stents, with an impressive clinical success rate comparable to EVT outcomes. The VACStent offers a new option for clinical treatment of critical situations in esophageal perforations and anastomotic sutureline failures.

Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy (FALCON): an international multicentre randomized controlled trial.

AIM: To assess the added value of Near InfraRed Fluorescence (NIRF) imaging during laparoscopic cholecystectomy. METHODS: This international multicentre randomized controlled trial included participants with an indication for elective laparoscopic cholecystectomy. Participants were randomised into a NIRF imaging assisted laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. Primary end point was time to 'Critical View of Safety' (CVS). The follow-up period of this study was 90 postoperative days. An expert panel analysed the video recordings after surgery to confirm designated surgical time points. RESULTS: A total of 294 patients were included, of which 143 were randomized in the NIRF-LC and 151 in the CLC group. Baseline characteristics were equally distributed. Time to CVS was on average 19 min and 14 s for the NIRF-LC group and 23 min and 9 s for the CLC group (p 0.032). Time to identification of the CD was 6 min and 47 s and 13 min for NIRF-LC and CLC respectively (p < 0.001). Transition of the CD in the gallbladder was identified after an average of 9 min and 39 s with NIRF-LC, compared to 18 min and 7 s with CLC (p < 0.001). No difference in postoperative length of hospital stay nor occurrence of postoperative complications was found. ICG related complications were limited to one patient who developed a rash after injection of ICG. CONCLUSION: Use of NIRF imaging in laparoscopic cholecystectomy provides earlier identification of relevant extrahepatic biliary anatomy: earlier achievement of CVS, cystic duct visualisation and visualisation of both cystic duct and cystic artery transition into the gallbladder.

[Dental rehabilitation in a young patient with glycogen storage disease type 1B]. / Dentale rehabilitatie bij jonge patiënt met glycogeenstapelingsziekte type 1B.

A young woman, known to have glycogen storage disease type 1B (GSD1B) presents with severe periodontitis. GDS1B causes decreased hepatic and renal glucose production and in many cases neutropenia and neutrophil dysfunction leading to recurrent infections. It was decided to treat the patient by extraction of the most affected teeth and retention of the remaining teeth through periodontal treatment, both with antibiotic prophylaxis. After a follow-up period of 1.5 years, during which there was no visible improvement, it was decided to do a full dental extraction and fabricate complete dentures. Due to subsequent bone resorption in both jaws, the dentures were not functional. After consulting the internist and the oral and maxillofacial surgeon, the decision was then made to place dental implants in both the upper and lower jaw for implant-supported prosthetics. After successful treatment and an osseointegration period, the prosthetics were placed. 1 year after placement, there is a stable implantological situation, without pockets or apparent bone loss. The start of SGLT2 medication may have played a significant role in this.

[Cosmetic injectables in dental practice: legal aspects in the Netherlands]. / Cosmetische injectables in de tandheelkundige praktijk: juridische aspecten in Nederland.

A recent survey indicates 49% of this journal's subscribers endorse the administration of cosmetic injectables by properly trained dentists. Given the surging demand for cosmetic treatments, it's essential to establish clear guidelines and conventions defining the roles of the various healthcare professionals in various situations. There is, however, considerable discussion still and from a legal standpoint, the role of dentists within cosmetic medicine remains ambiguous. Under the Dutch Individual Healthcare Professions Act (Wet BIG), dentists are authorized to administer cosmetic injectables exclusively for dental purposes. However, based on the content of current dental training, one might argue that dentists' authorization could be extended to include facial injectable treatments in the entire face, in future. Presently, it is prudent for general practice dentists to abstain from cosmetic procedures with cosmetic injectables without a specific (aesthetic) dental objective.

Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study.

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.

Mainstream germline genetic testing for patients with epithelial ovarian cancer leads to higher testing rates and a reduction in genetics-related healthcare costs from a healthcare payer perspective.

OBJECTIVE: Germline genetic testing is increasingly offered to patients with epithelial ovarian cancer by non-genetic healthcare professionals, so called mainstream genetic testing. The aim of this study was to evaluate the effect of implementing a mainstream genetic testing pathway on the percentage of newly diagnosed patients with epithelial ovarian cancer to whom genetic testing was offered and the genetics-related healthcare costs. METHODS: The possible care pathways for genetic counseling and testing and their associated costs were mapped. Patient files from all newly diagnosed patients with epithelial ovarian cancer before (March 2016 - September 2017) and after (April 2018 - December 2019) implementing our mainstream genetic testing pathway were analyzed. Based on this analysis, the percentage of newly diagnosed patients to whom genetic testing was offered was assessed and genetics-related healthcare costs were calculated using a healthcare payer perspective based on a Diagnosis-Related Group financing approach. RESULTS: Within six months after diagnosis, genetic testing was offered to 56% of patients before and to 70% of patients after implementation of our mainstream genetic testing pathway (p = 0.005). Genetics-related healthcare costs decreased from €3.511,29 per patient before implementation to €2.418,41 per patient after implementation of our mainstream genetic testing pathway (31% reduction, p = 0.000). CONCLUSION: This study shows that mainstream genetic testing leads to a significantly higher proportion of newly diagnosed patients with epithelial ovarian cancer being offered germline genetic testing. In addition, it significantly reduces genetics-related healthcare costs per patient.

[Criminal behavior in frontotemporal dementia and Alzheimer's disease]. / Delinquentes Verhalten im Rahmen frontotemporaler Demenzen und der Alzheimer-Erkrankung.

Criminal behavior in older people represents a rare phenomenon. Among older criminals there are many first offenders and 75% are men. Dementia poses one possible origin of delinquency in advanced age. It is unclear how often dementia is the actual cause of delinquency in older age. In studies with older criminals the prevalence of dementia was heterogeneous due to methodological study issues. In the course of the disease 50% of patients with frontotemporal dementia and 10% of patients with Alzheimer's disease commit crimes. The neurobiological origin of delinquency in dementia is poorly understood. On the basis of current study results first delinquency in older age can be explained by impairment of social cognition, difficulties in making appropriate emotional contributions and disturbed control of behavior. Affection of frontal and anterior temporal brain structures seem to be of high relevance. As dementia impairs criminal responsibility psychiatrists are confronted with a forensic evaluation of legal culpability of older criminals. Regarding different etiologies of dementia, specific peculiarities need to be considered in a forensic psychiatric assessment. Especially frontotemporal dementia predisposes towards a wide spectrum of criminal behavior whereas patients with Alzheimer's disease predominantly commit crimes due to cognitive impairment. The review summarizes the present knowledge about criminal behavior in the context of dementia.

[Patient-specific joint prothesis for ankylotic temporomandibular joints]. / Individueel vervaardigde prothesen voor ankylotische kaakgewrichten.

A 49-year-old woman who suffered from severe obstructive sleep apnea (OSA) was referred to the department of Oral-, Maxillofacial Surgery department due to progressive limitation of the mouth opening and chronic pain in both temporomandibular joints. Based on clinical and radiological examinations, the patient was diagnosed with recurrent ankylosis of the temporomandibular joints. The patient was treated with 2 patient-specific implants of the temporomandibular joint combined with a Le Fort I osteotomy, and a genioplasty including a genioglossus advancement. This treatment may have advantages for the patient such as a lower recurrence rate of ankylosis, improved maximal mouth opening, pain reduction and improved aesthetic results.

Conservative treatment versus elective repair of umbilical hernia in patients with liver cirrhosis and ascites: results of a randomized controlled trial (CRUCIAL trial).

PURPOSE: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. METHODS: Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. RESULTS: Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI - 0.87 to 24.77; MCS 10.04, 95% CI - 2.78 to 22.86). CONCLUSION: This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01421550, on 23 August 2011.

[Intra-oral Perineurioma, a case report]. / Perineurioma: een zeldzame intraorale wekedelentumor.

A 48 year old woman was referred by her general practitioner to an oral and maxillofacial surgeon because of an asymptomatic, slow growing intra-oral tumor since three years. There were no sensory and motor symptoms. A well-defined tumor of 5 cm in diameter was located in the right cheek between the zygomaticus arch and the labial commissure. The skin and the intra-oral mucosa were intact without any change in colour or texture. The MRI showed a solitary mass with benign characteristics. A transoral radical excisional biopsy was performed under general anesthesia. Histopathological examination revealed a rare soft tissue perineurioma tumor.

Citius, Altius, Fortius.

2020 is a leap year. That means that we have one day extra and, if the Olympic games had survived the corona crisis, we would all be watching television and ask the eternal question whether Olympic records will for ever be broken and broken again, or that there are limits to human biology1 . In this article we ask the same question, but rather than discussing aspects of Citius, Altius, and Fortius of athletes we will discuss them for macromolecules. It is remarkable how many parallels can be found between Olympic records in these two seemingly different worlds. People involved in structure validation and re-refinement try to make us believe that most aspects of macromolecular structures can be caught by a number that has some constant value with little variation around it. We will show here that the PDB2 databank proves this idea to be wrong. In the protein structure world, it holds for many that "participating is more important than winning", but some, fortunately, still go for the record books.

Cost-effectiveness of sigmoid resection with primary anastomosis or end colostomy for perforated diverticulitis: an analysis of the randomized Ladies trial.

BACKGROUND: Several studies have been published favouring sigmoidectomy with primary anastomosis over Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis (Hinchey grade III or IV), but cost-related outcomes were rarely reported. The present study aimed to evaluate costs and cost-effectiveness within the DIVA arm of the Ladies trial. METHODS: This was a cost-effectiveness analysis of the DIVA arm of the multicentre randomized Ladies trial, comparing primary anastomosis over Hartmann's procedure for Hinchey grade III or IV diverticulitis. During 12-month follow-up, data on resource use, indirect costs (Short Form Health and Labour Questionnaire) and quality of life (EuroQol Five Dimensions) were collected prospectively, and analysed according to the modified intention-to-treat principle. Main outcomes were incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios, expressed as the ratio of incremental costs and the incremental probability of being stoma-free or incremental quality-adjusted life-years respectively. RESULTS: Overall, 130 patients were included, of whom 64 were allocated to primary anastomosis (46 and 18 with Hinchey III and IV disease respectively) and 66 to Hartmann's procedure (46 and 20 respectively). Overall mean costs per patient were lower for primary anastomosis (€20 544, 95 per cent c.i. 19 569 to 21 519) than Hartmann's procedure (€28 670, 26 636 to 30 704), with a mean difference of €-8126 (-14 660 to -1592). The ICER was €-39 094 (95 per cent bias-corrected and accelerated (BCa) c.i. -1213 to -116), indicating primary anastomosis to be more cost-effective. The ICUR was €-101 435 (BCa c.i. -1 113 264 to 251 840). CONCLUSION: Primary anastomosis is more cost-effective than Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis.

ANTECEDENTES: Se han publicado varios estudios en favor de la sigmoidectomía con anastomosis primaria (primary anastomosis, PA) sobre la intervención de Hartmann (Hartmann's procedure, HP) para la diverticulitis perforada con peritonitis purulenta o fecal (Hinchey grado III ó IV), pero apenas existe información de los resultados relacionados con el coste. Por lo tanto, el presente estudio tuvo como objetivo evaluar los costes y el coste efectividad del brazo DIVA en el ensayo clínico Ladies. MÉTODOS: Se realizó un análisis de coste-efectividad del brazo DIVA del ensayo clínico multicéntrico y aleatorizado Ladies, que comparó PA y HP para la diverticulitis Hinchey de grado III ó IV. Durante un seguimiento de 12 meses, se recogieron datos prospectivamente del uso de recursos, costes indirectos (SF-HLQ) y calidad de vida (EQ-5D), y se analizaron de acuerdo con una modificación del principio por intención de tratar. Los resultados principales fueron la relación coste-efectividad incremental (incremental cost-effectiveness ratio, ICER) y la relación coste-utilidad incremental (incremental cost-utility ratio, ICUR), expresados como la razón del incremento de costes y el incremento en la probabilidad de no requerir estoma o años de vida ajustados por calidad, respectivamente. RESULTADOS: En total, se incluyeron 130 pacientes, 64 de los cuales fueron asignados a PA (Hinchey III/IV: 46/20) y 66 a HP (Hinchey III/IV: 46/18). Los costes medios globales por paciente fueron más bajos para la PA (€20.544 (i.c. del 95%: 19.569 a 21.519)) en comparación con HP (€ 28.670 (i.c. del 95%: 26.636 a 30.704)), con una diferencia media de €−8.126 (i.c. del 95% −14.660 a −1.592)). Además, se observó un ICER de € −39.094 (95% bias-corrected and accelerated boodstrap confidence interval, BCaCI −1.213 a −116), lo que indica que PA es más coste efectiva. El ICUR fue € −101.435 (BCaCI del 95%: −1.113.264 a 251.840). CONCLUSIÓN: La anastomosis primaria es más rentable que el procedimiento de Hartmann para la diverticulitis perforada con peritonitis purulenta o fecal.

The value of cerebrospinal fluid α-synuclein and the tau/α-synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology.

BACKGROUND AND PURPOSE: Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well-defined, community-based cohorts and validated analytical methods, the diagnostic value of CSF total-α-synuclein (t-α-syn) alone and in combination with total tau (t-tau) in newly diagnosed patients with PD, DLB and AD was determined. METHODS: Cerebrospinal fluid concentrations of t-α-syn were assessed using our validated in-house enzyme-linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t-tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis. RESULTS: Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t-α-syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t-α-syn levels did not differ significantly between PD, DLB and AD. The t-tau/t-α-syn ratio showed an improved performance compared to the single markers. CONCLUSION: This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t-α-syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

A stepwise titration protocol for oral appliance therapy in positional obstructive sleep apnea patients: proof of concept.

PURPOSE: In patients with positional obstructive sleep apnea (POSA), oral appliance therapy (OAT) is among the first-line treatments. The aim of this study was to evaluate the effects of a new standardized stepwise titration protocol for OAT in a group of patients with POSA. METHODS: This was an observational intervention trial. Patients who were previously randomized to the OAT intervention arm of a comparison study comprised the subjects for this study. These patients, who had mild to moderate POSA, were assessed after 3 and 12 months for treatment efficacy, objective adherence by temperature microsensor, and side effects. The titration of OAT was performed using a standardized stepwise titration protocol including advancement levels of 60%, 75%, and 90% of the maximum mandibular protrusion. The optimal advancement level per individual was based on a weighted compromise between efficacy and side effects. RESULTS: In total, 36 patients were included and all completed the titration protocol after 3 months. At baseline, the OAT was set at 60% of the maximal mandibular protrusion position. At a 3-month evaluation, the advancement remained at 60% in 16 patients (44%) and reached 75% advancement in 20 patients (56%). Mean apnea-hypopnea index decreased from 12.9 events per hour (9.1-16.7) to 6.9 (3.7-10.3) (P < 0.001), and median objective adherence was 97.4 (61.4-100.00) after 3 months. The 12-month analysis showed consistent results and good OAT tolerance. Six patients (16.7%) terminated OAT and one patient (2.8%) was lost to follow-up. CONCLUSIONS: This standardized stepwise titration protocol for OAT showed good efficacy, good OAT tolerance, and good objective adherence in patients with mild to moderate POSA. Therefore, the protocol is recommended in research projects to improve standardization of methods between studies and in clinical practice for its practical feasibility.

Posterolateral plate fixation with Pantalarlock® is more stable than nail fixation in tibiotalocalcaneal arthrodesis in a biomechanical cadaver study.

BACKGROUND: Despite the promising results of ankle joint arthroplasty, the tibiotalocalcaneal (TTC) arthrodesis remains an established procedure in treatment of combined pathology of the ankle and subtalar joint. Despite the promising results in biomechanical investigations, nonunion rates of up to 24% are described in recent studies. The objective of this work was a comparative study of the biomechanical properties of the posterolateral plate fixation with retrograde intramedullary nail fixation. METHODS: Twenty four fresh-frozen human lower leg specimens (12 pairs) were used for the comparative biomechanical testing. Every specimen was preconditioned with 100 N over 200 cycles. After every 250 cycles the force was increased by 50 N from 200 to 600 N. This was followed by cyclic loading in dorsi-/plantiflexion with 800 N for 3000 cycles. All specimens were subjected to bone densitometry (DXA) and computed tomography. RESULTS: Significantly higher number of spacimens with nails (4) failed during the cycling testing in dorsi-/plantarflexion and futher two during the cyclic testing with 800 N. Two specimens with plates failed during the cyclic testing with 800 N. Statistical analysis showed that the specimens with the plate were significantly more stable in each test direction. The Pearson correlation demonstrated for the specimens with plate a linear relationship between the stiffness and the determined bone density. CONCLUSIONS: The results demonstrate a significantly superior stiffness of the Pantalarlock®-plate in all testing directions compared with the HAN nail. Probably the position of the plate on the tension side of the joint and the combination of locking and lag screws provide the higher stiffness of the plate system. The correlation of the stiffness with bone density leads to more predictable results of the plate arthrodesis. We hope for a reduction of the pseudarthrosis rate and shorten the postoperative treatment phase. The authors expect advantages in the treatment of high risk patients with severe deformity of the ankle, bone defects, neuropathic deformity, poor bone quality and osteoporosis.